Molecular Divergence upon EGFR-TKI Resistance Could Be Dependent on the Exon Location of the Original EGFR-Sensitizing Mutation

Autor: Roberto Serna-Blasco, Estela Sánchez-Herrero, Lucía Robado de Lope, Sandra Sanz-Moreno, Alejandro Rodríguez-Festa, Dunixe Ares-Trotta, Alberto Cruz-Bermúdez, Fabio Franco, Alfredo Sánchez-Hernández, María de Julián Campayo, Carlos García-Girón, Manuel Dómine, Ana Blasco, José M. Sánchez, Juana Oramas, Joaquim Bosch-Barrera, María Á. Sala, María Sereno, Atocha Romero, Mariano Provencio
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cancers, Vol 14, Iss 18, p 4446 (2022)
Druh dokumentu: article
ISSN: 2072-6694
DOI: 10.3390/cancers14184446
Popis: Tumor molecular profiling upon disease progression enables investigations of the tumor evolution. Next-generation sequencing (NGS) of liquid biopsies constitutes a noninvasive readily available source of tumor molecular information. In this study, 124 plasma samples from advanced EGFR-positive NSCLC patients, treated with a first-line EGFR tyrosine kinase inhibitor (EGFR-TKI) were collected upon disease progression. The circulating cell-free DNA (cfDNA) was sequenced using the Oncomine Pan-Cancer Cell-Free Assay™. Excluding EGFR mutations, the most frequently mutated gene was TP53 (57.3%), followed by APC (11.3%), FGFR3 (7.3%), and KRAS (5.6%). Different molecular alterations were observed upon disease progression depending on the location of the original EGFR-sensitizing mutation. Specifically, the detection of the p.T790M mutation was significantly associated with the presence of exon 19 mutations in EGFR (Fisher p-value: 0.028). All KRAS activating mutations (n = 8) were detected in tumors with EGFR mutations in exons 18 and 21 (Fisher p-value < 0.001). Similarly, mutations in NRAS and HRAS were more frequently detected in samples from tumors harboring mutations in exons 18 or 21 (Fisher p-value: 0.050 and Fisher p-value: 0.099, respectively). In conclusion, our data suggest that the mechanisms underlying EGFR-TKI resistance could be dependent on the exon location of the original EGFR-sensitizing mutation.
Databáze: Directory of Open Access Journals
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